Genomic DNA in healthy cells is normally confined within the nucleus of the cells. However, genomic DNA is released into the circulation during cell aging where cells undergo programmed cell death or apoptosis, or during early disease states. These circulating DNAs are often not detectable in healthy individuals because of the homeostatic ability to efficiently eliminate them from the circulation. Likewise, circulating DNA in individuals during early disease stage, such as during early tumorigenesis, do not express tumor specific markers in amounts high enough for early detection using currently available nucleic acid detection methods. Although circulating DNA from individuals in the early stage of tumor development may be higher than normal healthy individuals, there are currently no biomarkers that would discriminate between circulating DNA released as a result of tumorigenesis and normal cell aging in individuals. In addition, most if not all of the free circulating DNA is eliminated from the circulation using the same cell machinery as in healthy individuals.
Furthermore, in circumstances where individuals have been exposed to high levels of radiation, for example in a nuclear accident, or high levels of radiation and/or infectious agent in a bioterror attack, massive cell damage ensues resulting in high levels of genomic DNA being released into circulation. However, there is not currently available a method for an efficient, reliable and inexpensive means for detecting these individuals for the purpose of treating and quarantining these individuals from cross-contaminating individuals who have not been exposed to such agents.
Accordingly, there is a need in the art for methods and/or biomarkers useful for detecting and/or measuring the state or condition of a subject, especially based on genomic DNA released into circulation upon pathophysiological insults.